tbuckley/cabot-search huggingface dataset:
Acute myeloid leukemia with <i>KMT2Ar</i> and association with risk of bleeding and early mortality.
Authors: Daniel Nguyen, Jing Ning, Wei Qiao, Koji Sasaki, Hagop M. Kantarjian, Nicholas James Short, Branko Cuglievan, Naval Guastad Daver, Courtney Denton Dinardo, Elias Jabbour, Tapan M. Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Marina Konopleva, Michael Andreeff, Farhad Ravandi, Ghayas C. Issa
Journal: Journal of Clinical Oncology (2022)

7026 Background: Acute myeloid leukemia (AML) with rearrangement of KMT2A is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity. Methods: In a retrospective analysis, we compared causes and rates of early mortality following induction treatment between a cohort of adults with KMT2Ar AML (N=172) and an age-matched cohort of patients (pts) with normal karyotype (NK) AML (N=522). Results: The 30 and 60-day (60d) mortality in pts with KMT2Ar AML were significantly higher compared to those with NK AML, with rates of 10% (17/172 pts) and 15% (26/172 pts) in KMT2Ar AML vs 4% (20/522 pts) and 7% (38/522 pts) in NK AML, respectively ( P=0.004). Among those who died within 60d, the most common contributing cause in KMT2Ar was respiratory failure without a clear infectious etiology in 38% (10/26 pts) vs 11% (4/38 pts) in NK AML ( P=0.01). We found 42% (11/26 pts) with KMT2Ar AML who died within 60d were either diagnosed with or had high clinical suspicion for diffuse alveolar hemorrhage (DAH) that warranted empiric therapy vs 18% (7/38 pts) with NK AML ( P=0.05). Given the high occurrence of DAH in KMT2Ar AML, we set out to quantify bleeding events and recorded major and minor bleeds as defined by the International Society of Thrombosis and Haemostasis. We found 65% (17/26 pts) with KMT2Ar AML had at least one bleeding event vs 32% (12/38 pts) with NK AML ( P=0.01). There was a significantly higher frequent occurrence of major bleeds (rate ratio=6.22; P=0.005) and total bleeding events (rate ratio=4.5; P=0.001) in KMT2Ar AML vs NK AML. KMT2Ar was associated with disseminated intravascular coagulopathy (DIC), as 93% of evaluable pts (14/15 pts) vs 54% (7/13 pts) in NK AML had overt DIC before death. Longitudinal trajectories of DIC parameters of pts who died within 60d showed significantly higher prothrombin time levels ( P=0.008) in KMT2Ar. In a multivariate analysis, KMT2Ar and a monocytic phenotypic were the only independent predictors of any bleeding event in pts who died within 60d (OR 3.5, 95% CI 1.4-10.4, P=0.03; OR 3.2, 95% CI 1.1-9.4, P=0.04). Conclusions: KMT2Ar AML is associated with higher early mortality and an increased risk of bleeding and coagulopathy compared with NK AML. Early recognition and aggressive management of DIC and coagulopathy are important considerations that could mitigate the risk of death during induction treatment.[Table: see text]
When and how to deliver oncology supportive care resources: An adolescent and young adult perspective.
Authors: Betty Roggenkamp, Nupur Mittal, Lauren Rynar, Adam Duvall, Denisse Martinez, Jennifer Lynn McNeer, Linda Rivard, Gabrielle Roberts, Julia Stepenske, Stacy Sanford
Journal: Journal of Clinical Oncology (2022)

6569 Background: The Coleman Supportive Oncology Collaborative for Adolescents and Young Adults (CSOC AYA) is a multi-institution Chicago-based quality improvement collaborative consisting of representation from AYA-focused oncology teams at six hospitals and national patient advocacy organizations. Coping with cancer as an AYA is challenging given their complex and unique phases of life and dichotomy between pediatric and adult care. AYAs with cancer are a recognized underserved population within the cancer community and have unique supportive care needs that are often unmet. The CSOC AYA focuses on improving access to resources for supportive care. Methods: We implemented an online survey across six cancer treatment centers (5 academic, 1 community) engaging 50 AYAs. Participants were newly diagnosed (2), currently on treatment (18), or off treatment (30). Participant age range was representative of AYAs ( &lt; 18years: 2%, 18 – 24: 36%, 25 – 34: 55%, and 35-39: 7%). Reported race was 60% Caucasian, 10% Black, 18% Latino, 8% Asian, 2% American Indian, and 2% other. Questions were asked to inform which supportive resources were desired by patients, when the resources would be most useful during the care continuum, and the preferred methods to receive information. Results: Greater than 54% percent of respondents desire social/emotional resources and peer connection at diagnosis. During treatment and after treatment, &gt; 71% and &gt; 56% respectively, desire guidance regarding nutrition/diet and physical activity/exercise, in addition to social/emotional support and peer connection (See table). Preferred methods to receive information were identified: 72% via email or text, 60% in person, and 45% via a patient portal. Conclusions: The CSOC AYA survey identified the type of supportive care resources AYAs need, when they are wanted, and their preferred methods for receiving them. Optimizing accessibility and availability of supportive care resources can enable AYA self-management and has the potential to improve quality of life. These survey results will serve as the basis for a patient-facing online intervention implemented throughout the care continuum with the intent to improve supportive care access for AYAs with cancer. [Table: see text]
Genetic profile and survival outcomes in a modern cohort of patients with biliary tract cancers (BTC): Single center experience in New York City.
Authors: Anahat Kaur, Fernand Bteich, Patrik Brodin, Rafi Kabarriti, Sanjay Goel, Andreas Kaubisch
Journal: Journal of Clinical Oncology (2022)

e16157 Background: BTCs are the second most common primary hepatobiliary malignancy with rising incidence and mortality worldwide. Individual characterization of BTCs at a genomic level is critical to tailor management strategies. Currently available data stem from studies in predominantly White populations. We conducted a retrospective study to determine the demographic, clinical and survival profiles of patients with BTCs seen in our center, who had been tested for genomic alterations. Methods: We identified 69 patients with BTCs diagnosed between 2015-2022 who had tissue-based genomic results available. Chi-square test was used to compare frequency distributions. Univariate analysis with cox regression model and multivariate cox proportional hazards test were conducted. Kaplan-Meier curves were used to assess overall survival (OS). Results: Median age at diagnosis was 67 years and median follow-up time was 15.5 months. Racial and ethnic minority populations were highly represented with 41% Hispanic, 29% Black and 17% White patients. ECOG performance status (PS) ranged between 0-2 at diagnosis. Most patients (40%) had stage IV BTC, with intrahepatic cholangiocarcinoma (CCA) being most prevalent (48%). On univariate modeling, variables associated with a shorter OS were age (HR 1.03, 95% CI 1.00-1.07, p = 0.05) and ECOG PS of 2 (HR 7.03, 95% CI 1.49-33.3, p = 0.014). In a multivariate model, ECOG PS 2 was independently associated with a shorter OS. The most common mutations (N, %) found on NGS were TP53 (28, 41%), KRAS (13, 19%), ARID1A (11, 16%), PIK3CA (9, 13%), ERBB2 (5, 7%) and FGFR2 (5, 7%). Median tumor mutation burden (TMB) was 4 Mut/Mb, with 18.9% having hypermutated (≥10 Mut/Mb) BTCs. Potentially actionable targets were found in 40 (58%) patients, 5.8% of which received targeted therapies with a median OS of 27 months (median OS of entire cohort was 22.8 months). KRAS mutation was significantly less common in intrahepatic CCA compared to the other BTC subtypes (p = 0.016). Race or ethnicity were not found to have a significant association with mutation frequency (Table). TP53 and ARID1A mutations were associated with a trend towards reduced OS in univariable analysis, with HR = 1.46 (p = 0.29) and HR = 1.64 (p = 0.28) respectively. Conclusions: Extensive genomic diversity was observed among BTC patients in our center which serves a large minority population. Studies with larger sample size are required to expand our understanding of the genomic spectrum in BTCs, its therapeutic and survival implications. [Table: see text]
A novel clinical trials imaging network platform for RECIST 1.1, and related protocols run on standard radiology software: A pilot at multiple oncology centers.
Authors: Don Goldstein, Howard S. Hochster, Jyoti Malhotra, Alberto Goldszal, Levi Sokol
Journal: Journal of Clinical Oncology (2022)

e13552 Background: Oncologists face the following challenges with clinical trials imaging analysis: non-structured radiology reports, inconsistent lesion measurement between time points, time-consuming and error-prone manual calculations for clinical trials protocols, and lack of dedicated storage and auditable signoff. Clinical Trials Imaging Network (CTIN) is a novel clinical trials imaging platform that allows radiologists to provide oncologists with dedicated clinical trials imaging reads and calculations from non-proprietary standard radiology dictation and PACS software, using RECIST 1.1 and other tumor response criteria. It was piloted at several cancer centers between 2019 and 2021. Methods: An anonymous survey was sent out to the oncologist and research coordinators who have experience using the CTIN program. The survey was designed to gauge the effectiveness of the software. Questions asked included the decrease in turnaround time between initiation of scan and completion of research protocol calculations, and regarding the decrease in time the oncologists personally need to make calculations. Additionally, respondents were inquired regarding the accuracy of the data, and how much time they had to spend verifying the integrity of the data. Results: The survey was sent to approximately 150 recipients, with 32 respondents. 84.4% of respondents said they strongly agreed or agreed that there was a decreased turnaround time between scan initiation, and completion of research protocol calculations, and 15.6% neither agreed nor disagreed. 80% strongly agreed or agreed that there was a decreased time they personally performed the calculations. 25.0% said they saved less than 5 minutes per time point personally performing the calculations, 28.6% said 5-15 minutes, 23.4% 15 to 30 minutes, and 17.8% 30-60 minutes. Users were also asked regarding their time spend verifying the data. 64.5% of people spent less than 5 minutes per time point verifying the integrity and quality of the data. 19.4% spent 5-15 minutes, 12.9% spent 15-30 minutes, and 3.2% 30-60 minutes. No one spent greater than 60 minutes verifying the data. 65.6% of people strongly agreed that they were confident in the accuracy of the data, 25.0% agreed, and 9.4% neither agreed or disagreed. 90.6% of people said that they were very satisfied or satisfied with CTIN. Conclusions: We have piloted an approach to provide clinical trials imaging metrics to oncologists using non-proprietary technology that runs from any standard radiology voice recognition system and PACS. The majority of respondents agreed that they would recommend this system for its time-saving, automated calculation and ease of use, user features. The CTIN platform bridges the gap between general radiology reads and clinical trials imaging reads without the need for dedicated radiology software.
Reply to: Heart Rate Response in Obstructive Sleep Apnea: A Clue to Reveal Cardiovascular Benefit from Continuous Positive Airway Pressure?
Authors: Ali Azarbarzin, Andrey Zinchuk, Yüksel Peker, Scott A. Sands
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

propose new measures, we encourage them to ensure that their measures meaningfully capture OSA-specific risk and test whether treating OSA confers benefit in one group over another.We hope that, together, as a field, we will develop sound inclusion criteria for future CPAP trials, selecting patients whose physiologic data reveals high risk of adverse CV outcomes in OSA.
Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022
Authors: John P. Thornhill, Sapha Barkati, Sharon Walmsley, Juergen Rockstroh, Andrea Antinori, Luke B. Harrison, Romain Palich, Achyuta Nori, Iain Reeves, Maximillian S. Habibi, Vanessa Apea, Christoph Boesecke, Linos Vandekerckhove, Michal Yakubovsky, Elena Sendagorta, Jose L. Blanco, Eric Florence, Davide Moschese, Fernando M. Maltez, Abraham Goorhuis, Valerie Pourcher, Pascal Migaud, Sebastian Noe, Claire Pintado, Fabrizio Maggi, Ann-Brit E. Hansen, Christian Hoffmann, Jezer I. Lezama, Cristina Mussini, AnnaMaria Cattelan, Keletso Makofane, Darrell Tan, Silvia Nozza, Johannes Nemeth, Marina B. Klein, Chloe M. Orkin
Journal: New England Journal of Medicine (2022)

Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined.
Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970–2019: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Annie Haakenstad, Olivia Angelino, Caleb M S Irvine, Zulfiqar A Bhutta, Kelly Bienhoff, Corinne Bintz, Kate Causey, M Ashworth Dirac, Nancy Fullman, Emmanuela Gakidou, Thomas Glucksman, Simon I Hay, Nathaniel J Henry, Ira Martopullo, Ali H Mokdad, John Everett Mumford, Stephen S Lim, Christopher J L Murray, Rafael Lozano
Journal: The Lancet (2022)

Meeting the contraceptive needs of women of reproductive age is beneficial for the health of women and children, and the economic and social empowerment of women. Higher rates of contraceptive coverage have been linked to the availability of a more diverse range of contraceptive methods. We present estimates of the contraceptive prevalence rate (CPR), modern contraceptive prevalence rate (mCPR), demand satisfied, and the method of contraception used for both partnered and unpartnered women for 5-year age groups in 204 countries and territories between 1970 and 2019.
E3 ubiquitin ligase MAGI3 degrades c-Myc and acts as a predictor for chemotherapy response in colorectal cancer
Authors: Haibo Wang, Wenjing Yang, Qiong Qin, Xiaomei Yang, Ying Yang, Hua Liu, Wenxiu Lu, Siyu Gu, Xuedi Cao, Duiping Feng, Zhongtao Zhang, Junqi He
Journal: Molecular Cancer (2022)

Abstract Background Recurrence and chemoresistance constitute the leading cause of death in colorectal cancer (CRC). Thus, it is of great significance to clarify the underlying mechanisms and identify predictors for tailoring adjuvant chemotherapy to improve the outcome of CRC. Methods By screening differentially expressed genes (DEGs), constructing random forest classification and ranking the importance of DEGs, we identified membrane associated guanylate kinase, WW and PDZ domain containing 3 ( MAGI3 ) as an important gene in CRC recurrence. Immunohistochemical and western blot assays were employed to further detect MAGI3 expression in CRC tissues and cell lines. Cell counting kit-8, plate colony formation, flow cytometry, sub-cutaneous injection and azoxymethane plus dextran sulfate sodium induced mice CRC assays were employed to explore the effects of MAGI3 on proliferation, growth, cell cycle, apoptosis, xenograft formation and chemotherapy resistance of CRC. The underlying molecular mechanisms were further investigated through gene set enrichment analysis, quantitative real-time PCR, western blot, co-immunoprecipitation, ubiquitination, GST fusion protein pull-down and immunohistochemical staining assays. Results Our results showed that dysregulated low level of MAGI3 was correlated with recurrence and poor prognosis of CRC. MAGI3 was identified as a novel substrate-binding subunit of SKP1-Cullin E3 ligase to recognize c-Myc, and process c-Myc ubiquitination and degradation. Expression of MAGI3 in CRC cells inhibited cell growth, promoted apoptosis and chemosensitivity to fluoropyrimidine-based chemotherapy by suppressing activation of c-Myc in vitro and in vivo. In clinic, the stage II/III CRC patients with MAGI3-high had a significantly good recurrence-free survival (~ 80%, 5-year), and were not necessary for further adjuvant chemotherapy. The patients with MAGI3-medium had a robustly good response rate or recurrence-free survival with fluoropyrimidine-based chemotherapy, and were recommended to undergo fluoropyrimidine-based adjuvant chemotherapy. Conclusions MAGI3 is a novel E3 ubiquitin ligase by degradation of c-Myc to regulate CRC development and may act as a potential predictor of adjuvant chemotherapy for CRC patients. Graphical Abstract
A Fibrinogen‐Mimicking, Activated‐Platelet‐Sensitive Nanocoacervate Enhances Thrombus Targeting and Penetration of Tissue Plasminogen Activator for Effective Thrombolytic Therapy
Authors: Yu Huang, Jingxuan Jiang, Jie Ren, Yuanyuan Guo, Qianqian Zhao, Jia Zhou, Yuehua Li, Rongjun Chen
Journal: Advanced Healthcare Materials (2022)

Abstract The development of a fibrinolytic system with long circulation time, high thrombus targeting, efficient thrombus penetration, effective thrombolysis, and minimal hemorrhagic risk remains a major challenge. Herein, inspired by fibrinogen binding to activated platelets in thrombosis, this article reports a fibrinogen‐mimicking, activated‐platelet‐sensitive nanocoacervate to enhance thrombus penetration of tissue plasminogen activator (tPA) for targeted thrombolytic therapy. This biomimetic nanothrombolytic system, denoted as RGD‐Chi@tPA, is constructed by “one‐pot” coacervation through electrostatic interactions between positively charged arginine‐glycine‐aspartic acid (RGD)‐grafted chitosan (RGD‐Chi) and negatively charged tPA. Flow cytometry and confocal laser scanning microscopy measurements show targeting of RGD‐Chi@tPA to activated platelets. Controlled tPA release triggered by activated platelets at a thrombus site is demonstrated. Its targeted fibrinolytic and thrombolytic activities are measured in in vitro models. The pharmacokinetic profiles show that RGD‐Chi@tPA can significantly prolong circulation time compared to free tPA. In a mouse tail thrombus model, RGD‐Chi@tPA displays efficient thrombus targeting and penetration, enabling a complete vascular recanalization as confirmed by the fluorescence imaging, histochemical assay, and laser speckle contrast imager. Consequently, RGD‐Chi@tPA induces a substantial enhancement in thrombolysis with minimal hemorrhagic risk compared to free tPA. This simple, effective, and safe platform holds great promise for the development of thrombolytic nanomedicines.
Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRASG12D-mutated non-small-cell lung cancer
Authors: B Ricciuti, J V Alessi, A Elkrief, X Wang, A Cortellini, Y Y Li, V R Vaz, H Gupta, F Pecci, A Barrichello, G Lamberti, T Nguyen, J Lindsay, B Sharma, K Felt, S J Rodig, M Nishino, L M Sholl, D A Barbie, M V Negrao, J Zhang, A D Cherniack, J V Heymach, M Meyerson, C Ambrogio, P A Jänne, K C Arbour, D J Pinato, F Skoulidis, A J Schoenfeld, M M Awad, J Luo
Journal: Annals of Oncology (2022)
Long-term effects of selective fetal growth restriction (LEMON): a cohort study of neurodevelopmental outcome in growth discordant identical twins in the Netherlands
Authors: Sophie G Groene, Koen J J Stegmeijer, Ratna N G B Tan, Sylke J Steggerda, Monique C Haak, Femke Slaghekke, Arno A W Roest, Bastiaan T Heijmans, Enrico Lopriore, Jeanine M M van Klink
Journal: The Lancet Child & Adolescent Health (2022)
Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with <i>RAS</i> wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial.
Authors: Takayuki Yoshino, Jun Watanabe, Kohei Shitara, Hirofumi Yasui, Hisatsugu Ohori, Manabu Shiozawa, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Masamitsu Hihara, Junpei Soeda, Kouji Yamamoto, Kiwamu Akagi, Atsushi Ochiai, Hiroyuki Uetake, Katsuya Tsuchihara, Kei Muro
Journal: Journal of Clinical Oncology (2022)

LBA1 Background: PARADIGM is the first prospective trial to test the superiority of PAN vs. BEV in combination with standard doublet first-line chemotherapy for patients (pts) with RAS WT mCRC and left-sided primary tumors. Methods: This open-label, multicenter trial in Japan (NCT02394795) randomly selected pts with chemotherapy-naive RAS WT mCRC to PAN + mFOLFOX6 or BEV + mFOLFOX6. Overall survival (OS) as primary endpoint was hierarchically tested in patients with left-sided tumors, followed by those in the full-analysis set (FAS) population. Key secondary endpoints included progression-free survival (PFS), response rate (RR), and curative resection (R0) rate. Results: From May 2015 to June 2017, 823 pts were randomized; 12 did not receive protocol treatment and 9 were excluded due to major deviation of inclusion criteria. A total of 400 pts received PAN and 402 pts received BEV as FAS; 312 and 292 pts had left-sided primary tumors, respectively. OS was analyzed after 448 OS events in left-sided pts with a median follow-up of 61 months. PAN significantly improved OS vs. BEV in both populations: left-sided (HR, 0.82; 95.798% CI, 0.68-0.99, p = .031, which crossed the boundary of significance [0.042]), and FAS (HR, 0.84; 95% CI, 0.72-0.98; p = .030, with &lt; 0.05 as the boundary). Although PFS was comparable between treatment groups, RR and R0 resection rates were higher with PAN compared with BEV (Table). HR for OS in the right-sided population was 1.09. No new safety signal was observed. Conclusions: PAN significantly improved OS vs. BEV in combination with mFOLFOX6 in pts with RAS WT and left-sided mCRC, establishing a standard first-line combination regimen for this population. Clinical trial information: NCT02394795. [Table: see text]
Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study
Authors: Alexandre Louvet, Julien Labreuche, Christophe Moreno, Claire Vanlemmens, Romain Moirand, Cyrille Féray, Jérôme Dumortier, Georges-Philippe Pageaux, Christophe Bureau, Faïza Chermak, Christophe Duvoux, Dominique Thabut, Vincent Leroy, Nicolas Carbonell, Benjamin Rolland, Ephrem Salamé, Rodolphe Anty, Jérôme Gournay, Jean Delwaide, Christine Silvain, Valerio Lucidi, Guillaume Lassailly, Sébastien Dharancy, Eric Nguyen-Khac, Didier Samuel, Alain Duhamel, Philippe Mathurin, Christophe Berthot, Sylvie Claudet, Alexandre Doussot, Caroline Gérardin, Emilie Muel, Jean-Baptiste Hiriart, Delphine Degré, Thierry Gustot, Agnès Bonadona, Laure Bordy, Marie-Noelle Hilleret, Olivier Detry, Pierre Honoré, Nicolas Meurisse, Emmanuel Boleslawski, Dominique Deplanque, Mehdi El Amrani, Gilles Lebuffe, Guillaume Millet, Daphnée Soret, Stéphanie Truant, Domitille Erard-Poinsot, Sylvie Radenne, Stéphanie Faure, Eve Gelsi, Régine Truchi, Marika Rudler, Laëtitia Rouleau, Audrey Brenner, Hélène Larrue, Jean-Marie Péron, Marie-Angèle Robic, Teresa Antonini, Jean-Charles Duclos-Vallée
Journal: The Lancet. Gastroenterology & hepatology (2022)
Endoscopy International Open – recently published
Journal: Endoscopy (2019)

Comment on: Novel telemetric sensor capsule for EGD urgency triage: a feasibility studyEndosc Int Open 2019; 07(06): E774-E781DOI: 10.1055/a-0880-5312 Comment on: Gastric foveolar-type adenomas endoscopically showing a raspberry-like appearance in the Helicobacter pylori-uninfected stomachEndosc Int Open 2019; 07(06): E784-E791DOI: 10.1055/a-0854-3818 Comment on: Colorectal endoscopic submucosal dissection can be efficiently performed by a trainee with use of a simple traction device and expert supervisionEndosc Int Open 2019; 07(06): E824-E832DOI: 10.1055/a-0901-7113